Repositioning Candidate Details
| Candidate ID: | R0297 |
| Source ID: | DB00828 |
| Source Type: | approved |
| Compound Type: | small molecule |
| Compound Name: | Fosfomycin |
| Synonyms: | (-)-(1R,2S)-(1,2-Epoxypropyl)phosphonic acid; (1R,2S)-epoxypropylphosphonic acid; (2R-cis)-(3-Methyloxiranyl)phosphonic acid; 1R-cis-(1,2-epoxypropyl)phosphonic acid; cis-(1R,2S)-epoxypropylphosphonic acid; FCM; Fosfocina; Fosfomycin; L-cis-1,2-epoxypropylphosphonic acid; Phosphomycin; Phosphonemycin; Phosphonomycin |
| Molecular Formula: | C3H7O4P |
| SMILES: | C[C@@H]1O[C@@H]1P(O)(O)=O |
| Structure: |
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| DrugBank Description: | Fosfomycin was discovered in 1969 by scientists at the Spanish Penicillin and Antibiotics Company and is produced by _Streptomyces fradiae_. It may also be produced synthetically and is commercially available as the disodium salt for intravenous administration and as the calcium or trometamol salt for oral administration. In terms of chemical structure, fosfomycin is a phosphoenolpyruvate analog and contains a phosphonic group and an epoxide ring. Due to its ease of administration as a single 3-gram oral dose and desirable safety profile, fosfomycin has largely become a first-line therapeutic option for the treatment of uncomplicated urinary tract infections (UTIs) in females. Despite being FDA approved only for urinary tract infections, fosfomycin actually has a broad spectrum of activity and is active against both gram-positive and gram-negative bacteria. As such there is great interest in exploring the usefulness of fosfomycin for indications beyond the treatment of UTIs. |
| CAS Number: | 23155-02-4 |
| Molecular Weight: | 138.059 |
| DrugBank Indication: | Fosfomycin is indicated for the treatment of uncomplicated cases of cystitis caused by susceptible strains of _Escherichia coli_ and _Enterococcus faecalis_. Fosfomycin is not officially indicated for the treatment of pyelonephritis or perinephric abscess, although there have been reported cases of off-label usage in these situations. |
| DrugBank Pharmacology: | Although used primarily to treat urinary tract infections, fosfomycin has been shown to act synergistically with other antibiotics against clinically relevant bacteria. There is also growing interest in the potential of fosfomycin to treat more complex infections since it has retained activity against many difficult-to-treat strains of bacteria including methicillin-resistant _Staphylococcus aureus_ (MRSA) and multidrug-resistant enterobacteria. Further, since fosfomycin has a unique and singular mechanism of action, the risk of cross-resistance with other antibiotics is low. Fosfomycin also demonstrates immunomodulating properties. For example, the antibiotic may influence components of the acute inflammatory cytokine response and enhances neutrophil phagocytic destruction of pathogens. Fosfomycin penetrates biofilms effectively and is capable of not only reducing or eliminating microorganisms in biofilms but can also alter the biofilm structure. |
| DrugBank MoA: | Fosfomycin exerts its bactericidal effects by binding covalently to a cysteine in the active site of the UDP-N-acetylglucosamine enolpyruvyl transferase (MurA) enzyme, rendering it inactive. By preventing MurA from catalyzing the condensation of phosphoenolpyruvate (PEP) with UDP-N-acetylglucosamine (UNAG), fosfomycin inhibits the production of the peptidoglycan precursor UDP N-acetylmuramic acid (UDP-MurNAc). Ultimately, the first step of bacterial cell wall synthesis is disrupted. In _Escherichia coli_, fosfomycin gains entry into bacterial cells via two mechanisms: the L-alpha-glycerophosphate system and the hexose-6-phosphate transporter system. Fosfomycin also has important effects on cell adhesion. For example, the adhesion of bacterial cells to urinary epithelial cells is reduced in the presence of fosfomycin. The adhesion of _Streptococcus pneumoniae_ and _Haemophilus influenzae_ to respiratory epithelial cells is also reduced |
| Targets: | UDP-N-acetylglucosamine 1-carboxyvinyltransferase inhibitor |
| Inclusion Criteria: | Therapeutic strategy associated |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs | |
|---|---|---|---|---|---|
| S05 | Anti-inflammatory | inflammatory | Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor | Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; | Details |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name |
|---|
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I01 | 552 | Pneumonia | A lung disease that involves lung parenchyma or alveolar inflammation and abnormal alveolar filling with fluid (consolidation and exudation). It results from a variety of causes including infection with bacteria, viruses, fungi or parasites, and chemical or physical injury to the lungs. It is accompanied by fever, chills, cough, and difficulty in breathing. http://en.wikipedia.org/wiki/Pneumonia | disease of anatomical entity/respiratory system disease/ lower respiratory tract disease/lung disease | Details |
| I09 | 104 | Bacterial infectious disease | A disease by infectious agent that results_in infection, has_material_basis_in Bacteria. http://en.wikipedia.org/wiki/Pathogenic_bacteria | disease by infectious agent | Details |